Effect of statins on thoracic aortic disease: results from a meta-analysis and experimental data

Background Thoracic aortic aneurysms (TAAs) that progress to acute aortic dissections are often fatal. Numerous risk factors, such as smoking, uncontrolled hypertension, and dyslipidemia, lead to increased wall stress and adverse outcomes. Nowadays, there is no pharmacological treatment that can reduce or even halt TAA progression. Purpose To evaluate the effect of statins on TAA growth rate and outcomes in TAA patients using a meta-analysis approach and testing the anti-fibrotic effect of satins in an in vitro model. Methods A detailed search related to the effects of statins on TAA was conducted according to PRISMA guidelines. The qualitative and quantitative analyses of statin effects on TAA growth rate were performed on 4 studies including 1850 patients, and for statin impact on outcomes were performed on 3 studies (2867 TAA patients). In vitro, the anti-fibrotic effect of 6.6 μM Atorvastatin were tested on vascular smooth muscle cells (VMSC) isolated from tunica media of ascending thoracic aorta of patients with aneurysm. Results We observed significant positive effect of statins on TAA growth rate. In particular, patients under statin treatment showed a reduced growth rate difference in means of -0.36 (95%CI: -0.64, -0.08; p=0.013) compared with controls, patients that did not take statins. Regarding the outcomes, such as death, dissection, or rupture of the aorta, and the need for operative repair, statins exhibited a protective effect reducing the number of events in patients with TAA with a logarithmic odds ratio of -0.56 (95%CI: -1.06, -0.05; p=0.030) compared to controls. Our in vitro results highlighted that, in transforming growth factor beta 1 (TGF-β1) pro-fibrotic condition, VSMC expressed a significant lower amount of collagen type I alpha 1 chain (COL1A1) when treated with Atorvastatin (untreated: 2.66±0.23 fold increase; treated: 1.63±0.09 fold increase; p=0.014). Conclusions Statins show a protective effect on TAA growth rate and adverse outcomes in patients with TAA, and an anti-fibrotic property on VSMC. Due to their pleiotropic effects, statins should be considered as a valuable pharmacological strategy to prevent the progression of TAA.